A source with knowledge of the situation told Press Association Sport that two Blues supporters were believed to have been stabbed on Tuesday evening, following an earlier altercation in the Turkish city.
It is understood no serious injuries were sustained and Chelsea released a statement confirming the reports of trouble.
"Chelsea Football Club is aware of two incidents involving fans in the city last night," read the statement on the club's official website, www.chelseafc.com.
"The club is working with all relevant agencies, including the police and the Foreign and Commonwealth Office, to best ensure the safety of all supporters."
English fans have been victims of violence in Istanbul before, with Leeds fans Christopher Loftus and Kevin Speight stabbed to death before a UEFA Cup tie in 2000.
The Foreign Office is investigating the latest flare-up, while the British Embassy in Ankara is in contact with Chelsea and the Turkish authorities over trouble. Ahead of Wednesday's match, Chelsea published revised advice from the UK Foreign and Commonwealth Office to supporters in Istanbul.
The body has warned fans about anti-government demonstrations taking place across Turkey, telling fans to "keep up to date with developments, be vigilant and avoid any protests or demonstrations".
Furthermore, Blues supporters have been urged to not use the Metro to get to and from the Turk Telecom Arena for the first-leg tie.
The club said: "The police have advised it is not safe for Chelsea supporters to use the Metro to and from the stadium on match day and it is strongly recommended use is made of the special bus services which will be provided for visiting supporters."
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